What are the symptoms and treatment options for copper deficiency?

Copper Deficiency: Clinical Manifestations and Management

Primary Clinical Manifestations

Copper deficiency primarily presents with hematologic abnormalities (anemia, neutropenia, leukopenia) and myeloneuropathy, with neurological symptoms often being irreversible if treatment is delayed. 1, 2, 3

Hematologic Symptoms

• Anemia (often macrocytic) is one of the most common presenting features 4, 5, 6
• Neutropenia and leukopenia frequently accompany the anemia 5, 3, 6
• Pancytopenia may occur in severe cases 6
• These hematologic disturbances typically correct with copper supplementation 4, 5

Neurological Symptoms

• Myeloneuropathy with prominent sensory ataxia and spastic gait is the hallmark neurological manifestation 3, 7
• Sensory deficits including decreased vibration sense, proprioception, and paresthesias in upper and lower extremities 4, 6, 7
• Progressive weakness affecting both upper and lower extremities 4, 5
• Gait abnormalities and ataxia that can be severe 5, 7
• Electrophysiological studies reveal axonal sensorimotor peripheral neuropathy 6, 7
• Spinal MRI may show increased T2 signal in the dorsal columns 7

Other Manifestations

• Impaired wound healing 1
• Cardiovascular, cutaneous, and immune system dysfunction 3

High-Risk Populations

Routine monitoring should be performed in patients after malabsorptive bariatric procedures, particularly gastric bypass surgery, as this has become the most frequent cause of severe acquired copper deficiency. 1, 2, 4, 5

At-Risk Groups Requiring Screening

• Patients following Roux-en-Y gastric bypass (RYGB) or other bariatric procedures 1, 2, 4, 5, 6
• Patients with short-bowel syndrome or other malabsorptive states 4, 3
• Patients with persistent diarrhea 1
• Patients taking excessive zinc supplementation (zinc induces intestinal metallothionein which blocks copper absorption) 8, 2, 3, 7
• Patients on prolonged parenteral nutrition or tube feeding 3
• Patients with unexplained anemia, neutropenia, or myeloneuropathy 1

When NOT to Screen Routinely

Routine monitoring is not recommended in the general population; copper levels should be evaluated only in symptomatic patients or those with specific risk factors 1

Diagnostic Approach

Laboratory Testing

• Measure plasma copper simultaneously with C-reactive protein (CRP), as inflammation falsely elevates copper levels since ceruloplasmin is an acute phase reactant 2
• Always check both zinc and copper levels together when evaluating for deficiency, as high zinc is a common cause of copper deficiency 8, 2
• Severe copper deficiency is defined as plasma copper <8 μmol/L (approximately <50 μg/dL) 2
• Normal copper level in one case report was 81 μg/dL after correction 4

Critical Diagnostic Pitfall

Do not assume normal copper levels if CRP is elevated, as ceruloplasmin (which carries copper) is an acute phase reactant and will be falsely elevated during inflammation 2

Treatment Guidelines

Therapeutic Dosing for Established Deficiency

For copper deficiency myelopathy, initiate treatment with 4-8 mg of copper daily, which is substantially higher than standard supplementation doses (1-3 mg daily used for prevention). 2, 3

Route of Administration

• Intravenous copper repletion should be considered for rapid correction in cases of severe neurological symptoms or when oral therapy fails 2, 5, 3
• One case report demonstrated correction from 39 to 81 μg/dL after 5 days of IV trace elements within parenteral nutrition 4
• Combined intravenous and oral supplementation followed by oral copper alone can normalize serum levels 5
• For severe copper deficiency (plasma copper <8 μmol/L), repletion measures must be taken immediately, regardless of CRP elevation 2

Maintenance and Prevention

• Standard post-bariatric supplementation provides only 1-3 mg copper daily, which is insufficient for treating established deficiency but appropriate for prevention 2
• Do not use standard supplementation doses (1-3 mg daily) to treat established deficiency—these are prophylactic doses only 2

Zinc-Copper Balance

• Maintain a ratio of 8-15 mg zinc to 1 mg copper when supplementing both minerals therapeutically 8, 2
• Do not supplement copper without checking zinc levels first, as the interaction between these minerals is bidirectional 2
• If taking zinc supplements, separate copper administration by several hours to minimize direct competition at the intestinal level 8

Monitoring Response to Treatment

• Recheck levels after 3 months of supplementation for mild deficiencies 8, 2
• If copper levels fall during zinc supplementation, referral for specialist advice is recommended 8

Prognosis and Critical Warnings

Neurological Outcomes

Neurological manifestations of copper deficiency may be irreversible even with treatment, while hematological disturbances typically correct with supplementation. 4, 5, 3

• Hematologic indices often correct rapidly with IV copper repletion 5
• Neurological deficits may show only partial resolution even with aggressive treatment 5
• However, significant neurological improvement is possible, particularly if treatment is initiated within 8 months of symptom onset 7
• Early recognition and treatment may prevent neurological deterioration but improvement is often slight and inconstant 7

Urgent Action Required

Do not delay treatment waiting for specialist referral in severe cases—initiate copper replacement immediately while arranging follow-up. 2

Key Clinical Pitfall

Copper deficiency myeloneuropathy is virtually indistinguishable from subacute combined degeneration due to vitamin B12 deficiency, and co-occurrence of multiple micronutrient deficiencies is common, making diagnosis challenging 6